rs779092602
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001242.5(CD27):c.541C>T(p.Gln181Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001242.5 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD27 | NM_001242.5 | c.541C>T | p.Gln181Ter | stop_gained, splice_region_variant | 5/6 | ENST00000266557.4 | |
CD27-AS1 | NR_015382.2 | n.621G>A | non_coding_transcript_exon_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD27 | ENST00000266557.4 | c.541C>T | p.Gln181Ter | stop_gained, splice_region_variant | 5/6 | 1 | NM_001242.5 | P1 | |
CD27-AS1 | ENST00000689782.1 | n.100+572G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251028Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135744
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727232
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Lymphoproliferative syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 08, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 540910). This variant has not been reported in the literature in individuals affected with CD27-related conditions. This variant is present in population databases (rs779092602, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln181*) in the CD27 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CD27 are known to be pathogenic (PMID: 25843314). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at